Up until FY 2008, the ID09B time-resolved X-ray beamline at the European Synchrotron and Radiation Facility (ESRF) in Grenoble, France was the only facility in the world capable of acquiring time-resolved macromolecular structures with 150-ps time resolution and <2-Angstrom spatial resolution. Over the past decade, the Anfinrud group has been instrumental in helping develop this capability at the ESRF. Our effort has involved the design of X-ray shutters and choppers, timing electronics based on a Field-Programmable-Gate-Array (FPGA), and laser systems. During that era, the ESRF operated in a mode that was optimized for our time-resolved Laue crystallography studies only 14 days out of each year, and we had access to only a portion of this limited amount of beam time. To expand the amount of beam time available for our studies, we partnered with the Advanced Photon Source (APS) in Argonne, IL and BioCARS to develop picosecond time-resolved X-ray capabilities on Sector 14 at the APS. BioCARS is an NIH-funded beamline headed by Prof. Keith Moffat, and is operated by the University of Chicago. In FY2005, Dr. Marvin Gershengorn, Director of Intramural Research at NIDDK, committed in excess of $1M to procure the capital equipment needed for this effort. Our vision was to achieve picosecond time-resolved X-ray capabilities comparable to that realized at the ESRF while the APS is operated in 24-bunch mode, a common operating mode that is used 132 days per year. This goal required that we isolate a single bunch of X-rays from a train of pulses separated by only 153 ns. To that end, we upgraded a high-speed X-ray chopper with new, low phase-noise electronics and a new, specially designed rotor. Our BioCARS collaborators upgraded their X-ray optics and developed a heat-load chopper, both of which were essential to these efforts. In July 2007, we succeeded in isolating a single bunch of X-rays during their 24-bunch mode, albeit at low X-ray flux due to safety concerns. To achieve X-ray fluence comparable to that generated at the ESRF when they operate in their exotic 4-bunch mode, we replaced the existing U33 undulator (33-mm magnetic period) with two newly designed U23 and U27 undulators. When the gaps of these undulators are tuned to generate 12-keV X-ray photons, the X-ray fluence exceeds that generated at the ESRF during their 4-bunch mode. When the APS operates in their exotic hybrid mode, which is scheduled approximately 31 days per year, the X-ray fluence is a factor of 4 higher than that available with the ESRF 4-bunch mode. For safety reasons, we were not allowed to use both undulators in tandem until Nov. 2007. The infrastructure needed to pursue picosecond time-resolved X-ray studies goes far beyond delivering single X-ray pulses to the experimental hutch. We installed a picosecond laser system in a laser hutch located near the X-ray hutch, and have installed an array of laser diagnostics that aid in the optimization of the laser performance. We have also developed an FPGA-based timing system that synchronizes all time-critical components to the X-ray pulses. For example, the FPGA drives the heat-load chopper, the high-speed chopper, the picosecond laser system, a millisecond shutter, and various other motion controls that must be synchronized with the experiment. Importantly, we can set the time delay between X-ray and laser pulses from picoseconds to seconds with a precision of 10 ps. We also developed the diffractometer used to acquire time-resolved X-ray diffraction images. This effort included the design of a millisecond shutter, a motorized support for the high-speed X-ray chopper, a support for motorized X-ray slits, detectors for non-invasively monitoring the laser and X-ray pulse energy and relative time delay, a motorized stage for the X-ray detector, supports for a collimator pipe and X-ray beam stop, beam conditioning optics that tailor the laser pulses in both space and time, beam delivery optics that focus the laser pulses onto the sample, motorized controls to center the focused laser pulse on the sample, and motorized controls to center the collimator pipe on the X-ray beam. We have recently incorporated a rapid translation stage for time-resolved WAXS studies, which allows us to integrate scattering patterns with a move-stop-acquire sequence that repeats at frequencies up to 41 Hz. Finally, we continue to develop the software required to control the beamline. This software package, written in Python, is generalized for both time-resolved Laue crystallography and time-resolved SAXS/WAXS studies. One recent challenge is the long-term instability of the X-ray and laser spot position. For example, our time-resolved Laue studies require precise overlap of the laser and X-ray beams along the top edge of a protein crystal. The X-ray position should be stable to about 10 um, a dimension that is about one-tenth that of a human hair. The laser beam needs to be stable to about 30 um. Unfortunately, the vertical X-ray focusing mirror suffers from drift that affects the position of the X-ray beam. In collaboration with BioCARS, we have developed a scheme to periodically measure the X-ray beam position and, if necessary, make an adjustment to recenter the beam. The laser beam position wanders as well, and this motion appears to be due to thermal drift outside the experimental hutch. We don't have direct control of the ambient temperature;instead, we are developing a non-invasive means to periodically assess the laser beam position and, if necessary, make an adjustment to recenter the beam. The ability to non-invasively monitor the laser and X-ray beam is quite beneficial. For example, at 23:22 on 23 Oct 2008, the X-ray timing suddenly shifted and arrived 60 ps too early. Thanks to the noninvasive X-ray timing monitor we designed into the time-resolved X-ray diffractometer, we could assign a time stamp to pulses used in time-resolved measurements, and could therefore detect this sudden shift. After communicating with the machine division of the APS, we learned that they shifted the phase of their injection by 60 ps, and the resulting timing error was uncompensated in the timing signal delivered to the individual beamlines. After reporting this event, they succeeded in developing an alternative method for shifting the phase that preserves the accuracy of the timing signal used by our FPGA-based timing electronics. Thus far, the problem hasnt recurred. Though we continue to refine beamline components as well as methodologies for acquiring time-resolved X-ray data, most of the components have been properly commissioned, and our focus is shifting to scientific problems.